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Prednisolone clearance at steady state in dogs
The Journal of Pharmacology and Experimental Therapeutics
|November 1, 1980
Summary
In dogs, prednisolone clearance slightly decreased with higher doses. The conversion of prednisolone to prednisone was found to be saturable, indicating a limited capacity for this metabolic process.
Area of Science:
- Pharmacokinetics
- Drug Metabolism
Background:
- Prednisolone dosing and clearance relationships require clarification, particularly under steady-state conditions.
- Understanding the saturability of prednisolone to prednisone conversion is crucial for predicting drug behavior.
Purpose of the Study:
- To investigate prednisolone clearance in dogs at steady-state across varying doses.
- To determine if the conversion of prednisolone to prednisone, mediated by 11 beta-hydroxydehydrogenase, is a saturable process.
Main Methods:
- Six dogs received zero-order infusions of prednisolone to achieve steady-state plasma concentrations.
- Prednisone, total, and free prednisolone levels were quantified using high-pressure liquid chromatography and equilibrium dialysis.
- Clearance values (total and unbound) were calculated based on infusion rates and steady-state concentrations.
Main Results:
- A slight but statistically significant decrease in both total and unbound prednisolone clearance was observed as prednisolone steady-state levels increased.
- The prednisolone to prednisone conversion demonstrated saturable kinetics, with a calculated Km of 658 ng/ml.
Conclusions:
- Prednisolone clearance in dogs does not increase with dose under steady-state conditions; it shows a slight decrease.
- The metabolic conversion of prednisolone to prednisone is a saturable process in dogs, suggesting potential for drug interactions or altered metabolism at higher concentrations.